Expression of interferon regulatory factor 4 in chronic myeloid leukemia: Correlation with response to interferon alfa therapy
| Autor: | Manuel Schmidt, Andreas Neubauer, Jutta Proba, Gerhard Ehninger, Rüdiger Hehlmann, Andreas Hochhaus, Georg J. Hoppe, Burghardt Wittig, Sven A. König-Merediz, Cornelia Brendel |
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| Předmět: |
Cancer Research
T-Lymphocytes Chronic myelomonocytic leukemia Alpha interferon Antineoplastic Agents Lymphocyte Activation Monocytes hemic and lymphatic diseases Leukemia Myelogenous Chronic BCR-ABL Positive medicine Tumor Cells Cultured Humans Lymphocytes RNA Messenger neoplasms Interferon alfa B-Lymphocytes Clinical Trials as Topic business.industry Myeloid leukemia Interferon-alpha Leukemia Myelomonocytic Chronic Precursor Cell Lymphoblastic Leukemia-Lymphoma medicine.disease Hematopoietic Stem Cells Leukemia Lymphocytic Chronic B-Cell Lymphocyte Subsets DNA-Binding Proteins Haematopoiesis Leukemia Cell Transformation Neoplastic Oncology Leukemia Myeloid Immunology Acute Disease Interferon Regulatory Factors Cancer research business Interferon regulatory factors IRF4 medicine.drug Transcription Factors |
| Zdroj: | Scopus-Elsevier |
| Popis: | PURPOSE: Mice experiments have established an important role for interferon regulatory factor (IRF) family members in hematopoiesis. We wanted to study the expression of interferon regulatory factor 4 (IRF4) in various hematologic disorders, especially chronic myeloid leukemia (CML), and its association with response to interferon alfa (IFN-α) treatment in CML. MATERIALS AND METHODS: Blood samples from various hematopoietic cell lines, different leukemia patients (70 CML, 29 acute myeloid leukemia [AML], 10 chronic myelomonocytic leukemia [CMMoL], 10 acute lymphoblastic leukemia, and 10 chronic lymphoid leukemia patients), and 33 healthy volunteers were monitored for IRF4 expression by reverse transcriptase polymerase chain reaction. Then, with a focus on CML, the IRF4 level was determined in sorted cell subpopulations from CML patients and healthy volunteers and in in vitro–stimulated CML cells. Furthermore, IRF4 expression was compared in the CML samples taken before IFN-α therapy and in 47 additional CML samples taken during IFN-α therapy. IRF4 expression was then correlated with cytogenetic response to IFN-α. RESULTS: IRF4 expression was significantly impaired in CML, AML, and CMMoL samples. The downregulation of IRF4 in CML samples was predominantly found in T cells. In CML patients during IFN-α therapy, a significant increase in IRF4 levels was detected, and this was also observed in sorted T cells from CML patients. The increase seen during IFN-α therapy was not due to different blood counts. In regard to the cytogenetic response with IFN-α, a good response was associated with high IRF4 expression. CONCLUSION: IRF4 expression is downregulated in T cells of CML patients, and its increase is associated with a good response to IFN-α therapy. These data suggest IRF4 expression as a useful marker to monitor, if not predict, response to IFN-α in CML. |
| Databáze: | OpenAIRE |
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